JPS5822150B2 - 3,4-dihydro-2H-pyran-3-one derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides novel 3,4-dihydro-2H-pyran-3-
Concerning on derivatives.

The compounds of this invention are useful as intermediates for 3-oxy-4H-pyran-4-ones, which are useful as flavoring agents added to foods.

For example, 2-methyl-3-oxy-4H-pyran-4-
On and H 2-ethyl-3-oxy-4H-pyran-4-
On is a well-known flavoring agent.

Since it is extremely important as a flavor improver for foods, methods for producing this substance have been reported in various fields.

For example, starting with Special Publication No. 110 of 1972, Special Publication No. 48-
No. 568, No. 48-68574 to 68576, etc. Also J,
Am, Chem, Soc, 682557~6B1946
), Li 2908-9 (1947), 70 2321-
5 (1948).

Various manufacturing methods are described in 5912-13 (1951) and the like.

However, all of these methods use raw materials that are difficult to obtain or involve complicated methods, resulting in low yields and cannot be said to be economical methods.

Moreover, all of these methods involve processing using 4H-pyran-4-ones as raw materials and intermediates, and they tend not to go beyond conventional synthetic thinking.

In view of the problems of the second class conventional method, the inventors have determined that (1) the starting materials are easily available and inexpensive, (2) the process is short and the reaction conditions are mild, and (3) the process is less polluting. (4) As a result of conducting research to meet the objectives such as being able to manufacture the final target product at a very low cost, we found that the above-mentioned 4.
Unlike conventional methods that use H-pyran-4-ones as raw materials and intermediates, 2H, which can be easily derived from furfural,
It has been found that the above object can be easily achieved by using -pyran-3-ones as a starting material.

That is, the present invention is based on the general formula [In the formula, R represents a methyl group or an ethyl group.

] 3,4-dihydro-2H-pyran-3-
Concerning on derivatives.

By converting the compound of the present invention into ml, the general formula [In the formula, R has the same meaning as above.

3-oxy-4H-pyran-4-ones represented by the following formula can be obtained.

The compound of the general formula [■] of the present invention is a new compound, for example, a known compound of the general formula [where R is the same as above, and R' is a hydrogen atom, a linear or branched Branched alkyl group or 1 carbon number
-6 linear or branched acyl group.

]5,6-sihydro2H--pyran-5
It is produced by hydrogenating a -one derivative to obtain a tetrahydropyran-5-one derivative represented by the general formula [wherein R and R' are the same as above], and then eliminating water or alcohol from the compound. The compound of formula 8 CI) is a known compound and can be obtained in high yield, for example, by the following reaction.

However, in the above formula, R and R' are the same as above, and R'' represents a straight chain or branched alkyl group having 1 to 4 carbon atoms.

That is, the compound of general formula (Iff) is obtained by electrolytically oxidizing furfuryl alcohol [■] in the presence of R″OH.
-By treating dialkoxy-furfuryl alcohol (Vl) with an acidic catalyst to carry out a ring expansion reaction,
Alternatively, it can be obtained by further acetalization or acylation.

As the hydrogenation catalyst used in the reaction (hydrogenation reaction) to hydrogenate the compound of formula U) to obtain the compound of formula (IV), commonly used hydrogenation catalysts such as expanded Raney nickel,
Stabilized Raney nickel, various types of nickel, copper-chromium,
Examples include various platinum catalysts, palladium-carbon catalysts, rhodium catalysts, iridium catalysts, ruthenium catalysts, and various cobalt catalysts.

As conditions for hydrogenation, either normal pressure or increased pressure can be adopted.

The reaction temperature is generally 0 to 150°C, preferably 20 to 50°C.Although this reaction can be carried out in a solvent or without a solvent, it is preferably in a solvent.

Examples of the solvent in the present invention include water and methanol.

Alcohols such as ethanol and isopropyl alcohol, ethers such as diisopropyl ether, tetrahydrofuran and dioxane, and halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride are used.

The amount of these solvents to be used is usually in the range of about 100 to 1,000 mounds per mole of the starting material.

All known methods can be applied to the dehydration or dealcoholization of the compound of formula (IV). For example, dehydration or dealcoholization of the compound of formula (IV) ) A compound of formula CD is easily produced by heating (preferably at a temperature near the boiling point of the organic solvent) a compound of formula CD.

Such compound CI) can be easily separated and recovered by commonly known methods.

Specifically, the compound of formula CI) prepared in this way is 2-methyl-3,4-dihydro 2H-pyran-3-
one and 2-ethyl-3,4-dihydro-2H-pyran-3-one.

By oxidizing the compound of the general formula (n) obtained as above, a compound represented by the general formula [■] is produced.

As the oxidation method used in the oxidation reaction, a wide variety of conventionally known oxidation methods can be used, such as treatment with selenium dioxide or selenite, treatment with nitrite in the presence of an acid, and treatment with air in the presence of a metal catalyst. Various methods such as oxidation treatment can be employed.

General formula [■] using selenium dioxide or selenite
In the method of oxidizing compounds, solvents used include aliphatic alcohols such as methanol, ethanol, propatool, and butanol, cellosolves such as methyl cellosolve, ethyl cellosolve, and butyl cellosolve, and cyclic ethers such as tetrahydrofuran and dioxane. Examples include mixed solvents of water and organic solvents such as the like.

The mixing ratio of the organic solvent and water is not particularly limited and can be used within a wide range, but it is preferably a ratio of 3 to 1 part by weight of water to 7 to 9 parts by weight of the organic solvent.

The amount of selenium dioxide or selenite to be used is not particularly limited and may be used in large excess, but it is usually 1.0 to 2.0 mol, preferably 1.1 to 1 mol, per 1 mol of the compound of general formula CI). .5 mol.

In the method of oxidizing the compound of general formula (1) using an acid and a nitrite ester, the solvent to be used is an aliphatic alcohol such as methanol, ethanol, propatool, or a mixture of a secondary alcohol and water. , ether, benzene, acetic acid, etc. can be used.

Specifically, nitrite esters include methyl nitrite, ethyl nitrite, propyl nitrite, impropyl nitrite, butyl nitrite, isobutyl nitrite, pentyl nitrite, inpentyl nitrite, hexyl nitrite, heptyl nitrite, Examples include octyl nitrite.

The amount of nitrite used is not particularly limited and may be used in large excess, but it is usually 1.0 to 2.0 times the mole of the compound of general formula [■], preferably 1.1 to 1. 5
It is twice the mole.

As the acid used with the nitrite ester, any acid, whether inorganic or organic, can be used as long as it hydrolyzes the nitrite to liberate nitrous acid and does not inhibit the progress of the reaction.

Among these, hydrochloric acid and sulfuric acid are preferred acids.

The amount of the acid used is usually 0.00% per mole of nitrite ester.
It is 1 to 2 times the mole, preferably 0.5 to 1.5 times the mole.

In these various oxidation reactions, the reaction temperature cannot be determined generally, but it is preferably carried out below the boiling point of the solvent, usually around 50 to 150°C (preferably 70 to 100°C).
It is.

The reaction time is usually 5 to 24 hours.

Compound (II) can be easily separated and recovered by generally known methods.

For example, after separating the reaction solution by filtration and removing the catalyst, it can be easily recovered by subjecting the p solution to vacuum distillation or column chromatography, or by purifying the concentrate by sublimation.

Specifically, the compounds produced as described above are 2-
Methyl-3-oxy-4H-pyran-4-one and 2-
Ethyl-3-oxy-4H-pyran-4-one.

In order to further clarify the present invention, reference examples and examples are listed below.

Reference example 1 2-methoxy-6-methyl-5,6-sihydro 2H-
14.8 g of pyran-5-one, 50 ml of methanol. and 5 g of stabilized nickel are introduced into a 500 cc capacity autoclave.

Next, 20 kg/cyj of hydrogen gas was introduced, and 50 kg/cyj of hydrogen gas was introduced.
Stirring at ~60°C absorbs the theoretical amount of hydrogen in 120 minutes.

After the reaction, excess hydrogen is removed, and the reaction solution is filtered to remove the catalyst.

When the P solution is concentrated under reduced pressure and the residue is distilled under reduced pressure at 16 mmHg, 2-methoxy-6-methyl-tetrahydropyran-5-one with a boiling point of 59 to 64°C is obtained as i4. i9 obtained.

Yield 94.5%. Reference example 2 2-ethoxy-6-ethyl-5,6-sihydro 2H-
17.1 g of pyran-5-one, 100 g of dioxane and 5 g of 5% palladium on carbon are introduced into a 500 CC capacity autoclave.

Next, 20 kg/i of hydrogen gas is introduced and stirred at room temperature to absorb the theoretical amount of hydrogen in 60 minutes.

After the reaction, excess hydrogen is removed, and the reaction solution is separated by tr to remove the catalyst.

The mud is concentrated under reduced pressure and the residue is distilled under reduced pressure at 12 mmHg to obtain 16.8 g of 2-ethoxy-6-ethyltetrahydropyran-5-one having a boiling point of 81 to 86°C.

Yield 97.3%. Example 1 2-methoxy-6-methyl-tetrahydropyran-5-
ON 14.3g, toluene 1007! and 1 g of p-toluenesulfonic acid were mixed and the reaction was carried out under reflux for 6 hours.

After the reaction is completed, the solvent toluene is distilled off under reduced pressure.

After washing the concentrated residue with dilute aqueous sodium bicarbonate solution, it is extracted three times with 50° each of ether.

After dehydrating the extract over magnesium sulfate, the ether extract is concentrated under reduced pressure.

The obtained concentrated residue is distilled under reduced pressure at 20 iiHg to obtain a fraction of 2-methyl-3,4-dihydro-2H at 85-90°C.
-8.4 g of pyran-3-one are obtained.

(corresponding to 76.3% of theoretical yield) Example 2 2-ethoxy-6-ethyl-tetrahydropyran-5-
17.2 g of toluene, 100 g of toluene, and 5 g of magnesium sulfate are reacted for 12 hours while stirring under reflux.

After the reaction is completed, the magnesium sulfate is removed and the F solution is concentrated under reduced pressure.

The concentrated residue was then distilled under reduced pressure at 20 miHg to give a fraction of 2-ethyl-3,4-dihydro-2 with a temperature of 87 to 92°C.
9.1 g of H-pyran-3-one are obtained.

(Corresponding to a theoretical yield of 72.6%) Reference Example 3 3.369 g of 2-methyl-3,4-dihydro-2H-pyran-3-one and 3.4 g of selenium dioxide were mixed with 2 ml of ethanol.
Heat under reflux for 8 hours in a solution consisting of 0 cc and 1 Q cc of water.

The selenium precipitate produced is filtered and the slurry is concentrated under reduced pressure.

After extracting the residue with chloroform, the chloroform layer is dehydrated with anhydrous magnesium sulfate.

After filtering off the magnesium sulfate, the filtrate is concentrated under reduced pressure to obtain light brown crystals as a residue.

If this crude product is recrystallized from benzene, the melting point is 158~
2.8 g of 2-methyl-3-oxy-4H-pyran-4-one having a temperature of 159 DEG C. is obtained as colorless crystals.

This corresponds to 75.1% of the theoretical yield.

Elemental analysis values: C57.2%, H4.8% (Theoretical values: C57.1%, H4.7%) The infrared absorption spectrum completely matches the standard.

Reference Example 4 3.78 g of 2-ethyl-3,4-dihydro-2H-pyran-3-one and 3.4 g of selenium dioxide were dissolved in ethanol 2
Heat under reflux for 8 hours in a solution consisting of 0 CC and IQ cc of water. 8 The produced selenium precipitate is filtered and the slurry is concentrated under reduced pressure.

After extracting the residue with chloroform, the chloroform layer is dehydrated with anhydrous magnesium sulfate.

After filtering off the magnesium sulfate, the r-liquid is concentrated under reduced pressure to obtain light brown crystals as a residue.

If this crude product is recrystallized from benzene, the melting point will be 90-9.
2-ethyl-3-oxy-4H-pyran- with 1°C
3.1 g of 4-one was obtained as colorless crystals.

C elemental analysis value corresponding to 75.2% of the theoretical yield C59
,9%, H5,8% (Theoretical value C60,0%, H5,7%) The infrared absorption spectrum completely matches the standard.Reference example
5 Mix 5.2 cc of concentrated hydrochloric acid with 200 cc of ethanol and
Heat to ℃ and stir.

11.5 g of ethyl nitrite was passed through this to give 3.36 g of 2-methyl-3,4-dihydro-2H-pyran-3-one.
A solution of 9 and 20 cc of ethanol was added dropwise over 30 minutes.

After further heating under reflux for about 5 hours, a concentrated aqueous sodium hydroxide solution was added to the reaction solution to adjust the pH to about 5 and exude inorganic crystals.
& filter.

The p solution is concentrated under reduced pressure and the residue is extracted with chloroform.

Cross the chloroform layer with anhydrous magnesium sulfate.

After removing magnesium sulfate, liquid F is concentrated under reduced pressure to obtain light brown crystals.

If the crude product is recrystallized from benzene, the melting point is 158-159.
2-Methyl-3-oxy-4H-pyran-4- with °C
2.3.9 is obtained as colorless crystals.

This corresponds to 64% of the theoretical yield.

The infrared absorption spectrum of the crystal is the same as that obtained in Reference Example 4.

Claims (1)

[Claims] 1. General formula [wherein R represents a methyl group or an ethyl group]. ] 3,4-dihydro-2H-pyran-3-
on derivatives.